Sex Differences in Middle Cerebral Artery Reactivity and Hemodynamics Independent from Changes in Systemic Arterial Stiffness in Adult Sprague-Dawley Rats

Young women are protected against cerebrovascular disease compared with men. However, the underlying mechanisms of sex differences in cerebrovascular function are not well understood. In this study, we determined whether sex differences in middle cerebral artery (MCA) reactivity are accompanied with changes in cerebral or systemic arterial resistance and stiffness in adult 25-week-old Sprague-Dawley (SD) rats. No differences in systolic or diastolic blood pressures were observed between sexes. Heart rate was higher in the female versus male SD. Left MCA pulsatility index (PI) was lower in female versus male SD, while no differences in left intracranial internal carotid artery (ICA) PI was observed between sexes. There were no differences in thoracic aorta or left common carotid artery pulse wave velocity (PWV) between sexes. In isolated MCA segments, female left MCA had lower contraction to potassium, but similar maximal contraction and sensitivity to thromboxane A2 receptor agonist U46619. Pre-incubation with indomethacin lowered maximal response and sensitivity to U46619 in male MCA but not female MCA suggesting that vasoconstrictor prostaglandins may have a greater role in male MCA vs. female MCA. Endothelial nitric oxide synthase (eNOS) and vascular smooth muscle layer thromboxane A2 receptor immunoreactivity were greater in female versus male SD. We conclude that sex differences in the MCA reactivity are associated with a differential functional profile of MCA in adult SD rats independent from changes in systemic PWV. NEW & NOTEWORTHYDespite the debilitating effects of cerebrovascular disease in women, the basis for sex differences in cerebrovascular dysfunction remains incompletely understood. Our study demonstrated that middle cerebral artery reactivity and hemodynamics are not accompanied by changes in central pulse wave velocity in mature adult Sprague-Dawley rats suggesting different mechanisms underlying baseline vascular reactivity of cerebral versus systemic arterial beds.